The oral spirochete, Treponema denticola (Td), is a putative etiologic agent in acute necrotizing ulcerative gingivitis, juvenile and adults periodontitis, and HIV-related periodontal diseases. The organisms display numerous potential virulence determinants; among these are collagenolytic and fibrinolytic activities, and inhibition of fibroblast and lymphocyte growth and function. Periodontitis patients have been shown to exhibit significantly elevated anti-Td IgG antibody titers when compared with healthy subjects. This immune reactivity has been exploited to facilitate the molecular cloning of Td antigens which are recognized by periodontitis patients. Sera from adult periodontitis patients reactive with Td laboratory strains were used to screen a genomic library of Td ATCC 35405 constructed in bacteriophage. Six distinct clones have been isolated, three of which correspond in molecular weight to immunoreactive proteins extracted from the outer sheath of the bacterium. The data indicate that the use of patients' sera to identify clones encoding for immunoreactive antigens of Td is a viable approach to study molecular aspects of Td structure and immune interactions in periodontal disease. These clones can be used to elucidate the molecular composition and function of Td antigens and to further an understanding of the role of Td and the host response to this bacterium in the pathogenesis of periodontal disease.